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福辛普利钠预处理联合缺血后处理对大鼠心肌缺血/再灌注损伤心脏的保护作用

[Protective effect of fosinopril sodium pretreatment combined with ischemic postconditioning on rat heart underwent myocardial ischemia/reperfusion injury].

作者信息

Zhang Da-wu, Zhang Lei, Liu Jian-gang, Wang Cheng-long, Shi Da-zhuo, Chen Ke-ji

机构信息

Department of Cardiology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing 100091, China.

出版信息

Zhonghua Xin Xue Guan Bing Za Zhi. 2010 Jul;38(7):633-7.

PMID:21055289
Abstract

OBJECTIVE

To investigate the effects of fosinopril sodium pre-treatment combined with ischemic postconditioning on rat serum and myocardial oxidative stress and proinflammatory cytokines post ischemia/reperfusion.

METHODS

Sixty Sprague-Dawley rats were randomly divided into sham group (n = 15), ischemia/reperfusion group (30 minutes in situ occlusion of the left anterior descending artery followed by 1 hour reperfusion, n = 15), IPoC group (30 minutes occlusion of the left anterior descending artery followed by 3 cycles of 10 seconds of reperfusion/10 seconds of ischemia before 1 hour reperfusion, n = 15) and fosinopril sodium group [pretreated with fosinopril sodium (0.9 mg×kg(-1)×d(-1) for 14 days) followed by IPoC protocol at 2 h after the last gavage, n = 15]. The arterial blood and heart samples were extracted after 1 hour reperfusion. Serum CK-MB and cTnT levels were detected by colorimetric method, myocardial infarction size was measured by nitrotetrazolium blue chloride staining, SOD content was examined by colorimetric method, MDA content was detected using thiobarbituric acid method, serum levels of Interleukin-1α (IL-1α), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were examined by radioimmunoassay, IL-1α, IL-6 and TNF-α levels of myocardial tissue were detected by ELISA.

RESULTS

Compared with I/R group, myocardial enzymes and infarction size were significantly decreased (P < 0.05, P < 0.01), serum SOD content was increased and MDA content was decreased (all P < 0.01), serum and myocardial levels of IL-1α, IL-6 and TNF-α were significantly reduced (P < 0.05, P < 0.05, P < 0.01) in IPoC group. Compared with IPoC group, fosinopril sodium pretreatment further reduced infarction size and myocardial enzyme CK-MB (P < 0.05), increased SOD content (P < 0.05) while reduced serum IL-6 and myocardial tissue TNF-α (P < 0.05, P < 0.01).

CONCLUSION

Pretreatment with fosinopril sodium enhanced the protective effect of IPoC on rat myocardium underwent I/R injury, possibly by reducing oxidative stress and early inflammatory reaction.

摘要

目的

探讨福辛普利钠预处理联合缺血后适应对大鼠缺血/再灌注后血清及心肌氧化应激和促炎细胞因子的影响。

方法

将60只Sprague-Dawley大鼠随机分为假手术组(n = 15)、缺血/再灌注组(左前降支动脉原位阻断30分钟,随后再灌注1小时,n = 15)、缺血后适应组(左前降支动脉阻断30分钟,随后在1小时再灌注前进行3个循环的10秒再灌注/10秒缺血,n = 15)和福辛普利钠组[用福辛普利钠(0.9 mg×kg⁻¹×d⁻¹,共14天)预处理,在末次灌胃后2小时按照缺血后适应方案处理,n = 15]。再灌注1小时后采集动脉血和心脏样本。采用比色法检测血清肌酸激酶同工酶(CK-MB)和心肌肌钙蛋白T(cTnT)水平,用氯化硝基四氮唑蓝染色法测量心肌梗死面积,比色法检测超氧化物歧化酶(SOD)含量,硫代巴比妥酸法检测丙二醛(MDA)含量,放射免疫法检测血清白细胞介素-1α(IL-1α)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,酶联免疫吸附测定法检测心肌组织中IL-1α、IL-6和TNF-α水平。

结果

与缺血/再灌注组相比,缺血后适应组心肌酶和梗死面积显著降低(P < 0.05,P < 0.01),血清SOD含量升高,MDA含量降低(均P < 0.01),血清及心肌中IL-1α、IL-6和TNF-α水平显著降低(P < 0.05,P < 0.05,P < 0.01)。与缺血后适应组相比,福辛普利钠预处理进一步减小梗死面积和降低心肌酶CK-MB(P < 0.05),增加SOD含量(P < 0.05),同时降低血清IL-6和心肌组织TNF-α水平(P < 0.05,P < 0.01)。

结论

福辛普利钠预处理增强了缺血后适应对缺血/再灌注损伤大鼠心肌的保护作用,可能是通过减轻氧化应激和早期炎症反应实现的。

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